Specific ligand binding on genetic variants of human α 1-acid glycoprotein studied by circular dichroism spectroscopy

TitleSpecific ligand binding on genetic variants of human α 1-acid glycoprotein studied by circular dichroism spectroscopy
Publication TypeJournal Article
Year of Publication2004
AuthorsFitos, I, Visy, J, Zsila, F, Bikádi, Z, Mády, G, Simonyi, M
JournalBiochemical Pharmacology
Volume67
Issue4
Pagination679 - 688
Date Published2004
KeywordsAcridine orange, Dicumarol, Genetic variants, Imipramine, Induced circular dichroism, α1-Acid glycoprotein
Abstract

Human α1-acid glycoprotein displays genetic polymorphism. Different drug binding properties of the two main genetic products (F1-S and A variants) have been demonstrated. In search for specific circular dichroism (CD) probes, dicumarol and acridine orange were found to specifically bind to the F1-S and A variants, respectively. Dicumarol binding to the F1-S variant produced induced Cotton effects originating from the favored chiral conformation of the bound label. Acridine orange gave induced biphasic Cotton effects due to chiral intermolecular exciton interaction between label molecules bound to the A variant. Displacement of the CD probes by specific marker ligands was demonstrated. The induced CD spectrum of dicumarol was found to change sign in the presence of imipramine, as a manifestation of high-affinity ternary complex formation on the F1-S variant. © 2003 Elsevier Inc. All rights reserved.

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